Abstract
Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are daily adjusted (entrained) by light via the retinohypothalamic tract (RHT). The RHT contains two neurotransmitters, glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP), which are believed to mediate the phase-shifting effects of light on the clock. In the present study we have elucidated the role of PACAP in light-induced phase shifting at early night in hamsters and shown that (i) light-induced phase delay of running-wheel activity was significantly attenuated by a specific PAC1 receptor antagonist (PACAP6-38) or by immunoblockade with a specific anti-PACAP antibody injected intracerebroventricularly before light stimulation; (ii) PACAP administered close to the SCN was able to phase-delay the circadian rhythm of running-wheel activity in a similar way to light; (iii) PACAP was present in the hamster RHT, colocalized with melanopsin, a recently identified opsin which has been suggested to be a circadian photopigment. The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP-expressing cells of the RHT.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies
-
Behavior, Animal
-
Circadian Rhythm / drug effects*
-
Circadian Rhythm / physiology
-
Cricetinae
-
Hypothalamus / physiology*
-
Immunohistochemistry
-
Light*
-
Male
-
Mesocricetus
-
Neural Pathways / chemistry
-
Neural Pathways / physiology
-
Neurons / drug effects
-
Neuropeptides / administration & dosage
-
Neuropeptides / analysis
-
Neuropeptides / immunology
-
Neuropeptides / pharmacology*
-
Neuropeptides / physiology*
-
Neurotransmitter Agents / analysis
-
Peptide Fragments / pharmacology*
-
Pituitary Adenylate Cyclase-Activating Polypeptide
-
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
-
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
-
Receptors, Pituitary Hormone / antagonists & inhibitors
-
Retina / chemistry
-
Retina / physiology*
-
Rod Opsins / drug effects
-
Rod Opsins / physiology
-
Running
-
Suprachiasmatic Nucleus / drug effects*
-
Synaptic Transmission / drug effects
Substances
-
Antibodies
-
Neuropeptides
-
Neurotransmitter Agents
-
Peptide Fragments
-
Pituitary Adenylate Cyclase-Activating Polypeptide
-
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
-
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
-
Receptors, Pituitary Hormone
-
Rod Opsins
-
melanopsin
-
pituitary adenylate-cyclase-activating-peptide (6-38)